Gold nanoparticles (GNPs) attract much interest because of their electronic, optical, thermal and catalytic properties as well as their biocompatibility and low toxicity, which have greatly impacted the biological fields of imaging, sensing and medicine in recent years (Jain et al., 2008) to detect chemicals in the sample, or microbes or particular molecules in the cells. However, GNPs only can achieve the specific sensitivity and detection limits. Energy is released by scattering if the molecules cannot absorb the photons' energy after the incident photons bombards to the molecules. Since most scattering belongs to Rayleigh scattering and Raman scattering accounts for 1/1000 of Rayleigh scattering, Raman scattering becomes the excellent tools for detecting molecular sensitivity and detection limits.
Surface enhanced Raman scattering (SERS) is a surface sensitive technique that results in effective enhancement of the Raman scattering for molecules in the vicinity of the surface of particles for 105˜106 times (Schatz, 1984). The most common application of combining SERS and GNP is to prepare the SERS nanoprobes which is to attach the Raman reporter onto the surface of metal nanoparticles, such as the thiol-related ligands bound to the surface of particles (Chompoosor et al., 2008; Hong et al., 2006). Several methods have been developed to stabilize the nanoprobes (i.e. nanoparticle-thiol molecule) by coating a shell, such as Silica (Mulvaney et al., 2003) and copolymers (Yang et al., 2009) onto the nanoprobes.
U.S. Pat. No. 7,333,197 discloses a flow cytometry based on Raman detection, wherein cells or particles are coated with a colloidal aggregate, the colloid-coated cells or particles are dispersed, and then the emitted surface enhanced Raman scattering is detected using the flow cytometry. However, cells or particles do not bound to the molecules carrying thiol signals, and cells or particles cannot completely separate individually, so as to result in the disturbance of signal detection.
Since the multiple nanoparticles are capped and usually aggregates in the prior art, the quantitative object to control the particular amount of nanoparticles cannot be achieved. Therefore, the technique which the single GNP is capped and can still represent Raman signal would be applied on the detection apparatus, would be applied on related detection for sera and cellular media containing salts or proteins, and have great benefit in the fields of biomedicine, medical diagnosis and environment.
It is therefore attempted by the applicant to deal with the above situation encountered in the prior art.